Recently, it has been reported that the natriuretic response to volume expansion induced by water immersion is diminished in diabetic patients. This altered sodium excretion in diabetic was not accountable by the hemodynamic changes or hormonal changes. These studies were unable to identify a specific mechanism for the altered volume reflex observed in diabetics. Recently, we have demonstrated that in diabetic rats, the natriuresis and diuresis produced by acute volume expansion is significantly blunted compared to control rats. In addition, renal denervation corrected this blunted natriuresis and diuresis in diabetic rats. These results suggest that part of the blunted natriuresis to volume expansion in the diabetic rats is mediated by an altered neural component of the volume reflex. There are several possible "intermediate steps" that could be altered in the neural component of the volume reflex. The present proposal is designed to determine: first, if the afferent limb of the volume reflex is altered; second, if decrease in norepinephrine released within the kidney in response to volume expansion is altered; third, if the end-organ response to renal sympathetic nerve stimulation is altered; and fourth, if renal alpha-1 adrenergic receptor density and coupling are altered in diabetic rats. The immediate significance of the studies proposed in this application is to gain insight into the mechanisms that cause the altered fluid and electrolyte balance during the early stage of diabetes. Once we understand the basic mechanisms that are involved, this information will enhance our ability to treat these complications in the diabetic state. The long-term significance and direction of future experiments will be to examine if alleviating this early sodium retention (e.g., by pharmacological means - blockage of specific alpha-1 receptor subtype) aids in reducing the later hemodynamic and cardiovascular problems observed in the diabetic state.